Pharmacokinetics, Tissue Distribution, and Anti-Lipogenic/Adipogenic Effects of Allyl-Isothiocyanate Metabolites

PLoS One. 2015 Aug 28;10(8):e0132151. doi: 10.1371/journal.pone.0132151. eCollection 2015.

Abstract

Allyl-isothiocyanate (AITC) is an organosulfur phytochemical found in abundance in common cruciferous vegetables such as mustard, wasabi, and cabbage. Although AITC is metabolized primarily through the mercapturic acid pathway, its exact pharmacokinetics remains undefined and the biological function of AITC metabolites is still largely unknown. In this study, we evaluated the inhibitory effects of AITC metabolites on lipid accumulation in vitro and elucidated the pharmacokinetics and tissue distribution of AITC metabolites in rats. We found that AITC metabolites generally conjugate with glutathione (GSH) or N-acetylcysteine (NAC) and are distributed in most organs and tissues. Pharmacokinetic analysis showed a rapid uptake and complete metabolism of AITC following oral administration to rats. Although AITC has been reported to exhibit anti-tumor activity in bladder cancer, the potential bioactivity of its metabolites has not been explored. We found that GSH-AITC and NAC-AITC effectively inhibit adipogenic differentiation of 3T3-L1 preadipocytes and suppress expression of PPAR-γ, C/EBPα, and FAS, which are up-regulated during adipogenesis. GSH-AITC and NAC-AITC also suppressed oleic acid-induced lipid accumulation and lipogenesis in hepatocytes. Our findings suggest that AITC is almost completely metabolized in the liver and rapidly excreted in urine through the mercapturic acid pathway following administration in rats. AITC metabolites may exert anti-obesity effects through suppression of adipogenesis or lipogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells
  • Acetylcysteine / metabolism
  • Adipogenesis / drug effects*
  • Administration, Oral
  • Animals
  • Gene Expression Regulation / drug effects
  • Glutathione / metabolism
  • Isothiocyanates / administration & dosage*
  • Isothiocyanates / pharmacokinetics*
  • Isothiocyanates / urine
  • Lipid Metabolism / drug effects*
  • Lipogenesis / drug effects*
  • Male
  • Mice
  • Oleic Acid / pharmacology
  • Rats
  • Tissue Distribution

Substances

  • Isothiocyanates
  • Oleic Acid
  • allyl isothiocyanate
  • Glutathione
  • Acetylcysteine

Grant support

This study was supported by a grant (E0143033653) from the Korea Food Research Institute of South Korea (www.kfri.re.kr). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.